Nicotinic acetylcholine receptor antagonistic activity of monoamine uptake blockers in rat hippocampal slices

Esteban C.P. Hennings, Janos P. Kiss, Karine De Oliveira, Peter T. Toth, E. Sylvester Vizi

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The aim of our study was to investigate the effect of different monoamine uptake blockers on the nicotine-evoked release of [3H]noradrenaline ([3H]NA) from rat hippocampal slices. We found that desipramine (DMI), nisoxetine, cocaine, citalopram, and nomifensine inhibit the nicotine-evoked release of [3H]NA with an IC50 of 0.36, 0.59, 0.81, 0.93, and 1.84 μM, respectively. These IC50 values showed no correlation with the inhibitory effect (K(i)) of monoamine uptake blockers on the neuronal NA transporter (r = 0.17, slope = 0.02), indicating that the NA uptake system is not involved in the process. In whole-cell patch clamp experiments neither drug blocked Na+ currents at 1 μM in sympathetic neurons from rat superior cervical ganglia, and only DMI produced a pronounced inhibition (52% decrease) at 10 μM. Comparison of the effect of DMI and tetrodotoxin (TTX) on the electrical stimulation- and nicotine-evoked release of [3H]NA showed that DMI, in contrast to TTX, inhibits only the nicotine-induced response, indicating that the target of DMI is not the Na+ channel. Our data suggest that monoamine uptake blockers with different chemical structure and selectivity are able to inhibit the nicotinic acetylcholine receptors in the CNS. Because these compounds are widely used in the therapy of depressed patients, our findings may have great importance in the evaluation of their clinical effects.

Original languageEnglish
Pages (from-to)1043-1050
Number of pages8
JournalJournal of neurochemistry
Volume73
Issue number3
DOIs
Publication statusPublished - Aug 30 1999

Keywords

  • Monoamine uptake systems
  • Nicotinic acetylcholine receptors
  • Selective serotonin reuptake inhibitors
  • Tricyclic antidepressants

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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